Cervical carcinoma, strongly associated with HPV 16 and 18, presents with abnormal vaginal bleeding and is characterised histologically by invasive squamous or glandular cells, and radiologically by a mass or thickening in the cervix.
Description
Cervical carcinoma is a malignant neoplasm of the cervix, the lowermost part of the uterus. It is the fourth most common malignancy among females globally. The disease is generally categorised into squamous cell carcinoma and adenocarcinoma types.
Pathogenesis
The development of cervical carcinoma is a multi-stage process that typically transitions through precancerous changes over a span of 10–20 years. The initial catalyst for this process is often persistent infection with high-risk strains of the human papillomavirus (HPV), particularly types 16 and 18. These high-risk HPV types integrate into the host genome, leading to overexpression of oncogenes E6 and E7, which in turn inhibit the tumour suppressor proteins p53 and retinoblastoma (Rb), respectively. This process culminates in dysplastic alterations in the cervical epithelium, progressing from low-grade cervical intraepithelial neoplasia (CIN) to high-grade CIN, carcinoma in situ, and eventually invasive carcinoma.
LSIL (Low-Grade Squamous Intraepithelial Lesion) and HSIL (High-Grade Squamous Intraepithelial Lesion) are terms used to describe cellular abnormalities in the cervix identified through a Pap smear or HPV test.
- LSIL corresponds to CIN 1 (Cervical Intraepithelial Neoplasia grade 1), which represents mild dysplasia confined to the basal 1/3 of the cervical epithelium. LSIL/CIN 1 is often associated with productive HPV (human papillomavirus) infections and can frequently regress to normal without treatment.
- HSIL comprises both CIN 2 and CIN 3. CIN 2 (moderate dysplasia) involves the basal 2/3 of the epithelium, while CIN 3 (severe dysplasia or carcinoma in situ) may involve more than 2/3 of the epithelium, extending up to full thickness. These stages represent more advanced precancerous changes with a greater risk of progression to invasive cervical cancer, particularly with persistent high-risk HPV infection.
Subtypes
Cervical carcinoma primarily includes two histologic subtypes which both arise from the squamocolumnar junction:
- Squamous cell carcinoma (70-90%): Usually originates from the squamocolumnar junction (area vulnerable to HPV infection).
- Adenocarcinoma (10-20%): Arises from the columnar epithelium of the endocervix.
Epidemiology, Risk Factors & Associations
- Most common gynaecologic malignancy worldwide, second most common in developing countries.
Risk factors include:
- HPV 16 and 18 infection (almost 99% of cases, 16 more common than 18). Other types associated with high-grade lesions include 31, 33 and 35.
- Low-risk types of HPV (types 6, 11) are rarely identified in high-grade lesions.
- Early sexual activity, multiple sexual partners
- Smoking
- Immunosuppression
- Co-infection with other sexually transmitted infections (like Chlamydia trachomatis and HIV)
- Long-term oral contraceptive use.
Clinical Features
- Early stages can be asymptomatic.
- As the disease progresses, women may experience abnormal vaginal bleeding, intermenstrual or post-coital bleeding, abnormal vaginal discharge, and pelvic pain.
- Advanced cases may present with urinary or rectal symptoms due to local invasion.
Complications
- Local invasion can result in bladder or rectal involvement, presenting with haematuria or rectal bleeding, respectively.
- Lymphatic spread is common, often involving the pelvic and para-aortic lymph nodes.
- Distant metastasis is less common but can involve the lungs, bone, and other organs.
Pathological Features
Histopathology
- Macroscopic: Cervical carcinoma can manifest as an exophytic or ulcerative mass, or as a diffuse infiltrative lesion causing cervical enlargement.
- Microscopic: Squamous cell carcinoma shows invasive nests of keratinising or non-keratinising squamous cells. Adenocarcinoma exhibits invasive glandular structures lined by malignant columnar cells.
Serology
- HPV DNA testing is crucial for screening and diagnosis.
Biochemistry
- Squamous cell carcinoma antigen (SCC-Ag) can serve as a tumour marker.
Radiological Features
General Features
- Cervical carcinoma characteristically demonstrates as a cervical mass or cervical wall thickening. Parametrial invasion, lymphadenopathy, or hydronephrosis may be seen in advanced stages.
CT
- Non-contrast: Lesion may be iso- to slightly hyperdense compared to the normal cervix.
- Contrast-enhanced: Enhances less than the normal cervix and may exhibit necrosis or cavitation.
MRI
- T1WI: The lesion appears iso- to hypointense compared to the normal cervix.
- T2WI: The lesion shows high signal intensity.
- T1 C+ (Gadolinium-enhanced): Lesion enhances less than the normal cervix.
- DWI/ADC: Restricted diffusion is usually noted due to high cellularity.
Grading and Staging
The FIGO (International Federation of Gynaecology and Obstetrics) system is used for staging cervical carcinoma, which considers tumour size, depth of invasion, and extent of spread.
Diagnosis
Diagnosis is typically made by cervical biopsy, often following abnormal Pap smear or HPV testing results. Definitive diagnosis requires histopathological examination.
Differential Diagnosis
- Endometrial carcinoma: Typically presents with postmenopausal bleeding and the lesion primarily involves the endometrium.
- Cervicitis: Inflammation of the cervix may mimic carcinoma but lacks the destructive invasion of malignant lesions.
Management
Management options include surgery (radical hysterectomy), radiotherapy, and chemotherapy. The choice depends on the stage of the disease, patient’s overall health status, and personal preferences. Post-treatment surveillance is essential due to the high rate of recurrence.